Human tissue factor pathway inhibitor-2 (TFPI-2), a 32 kDa Kunitz-type serine proteinase inhibitor, is primarily synthesized and secreted into the extracellular matrix (ECM) by a wide variety of cells including keratinocytes, dermal fibroblasts, endothelial cells, smooth muscle cells, and synoviocytes. Several lines of evidence suggest that TFPI-2 regulates the plasmin-mediated activation of matrix pro-metalloproteinases and plays a significant role in the regulation of ECM degradation, which is an essential step for tumor cell invasion and metastasis. TFPI-2, as well as a mutated first Kunitz-type domain (R24K KD1), also has been shown to induce caspase-mediated apoptosis in several tumor cell lines.